Development of Ultrasound Microbubbles and Phase Shift Microbubbles in Theranostics

Ultrasound is widely used for diagnostic imaging and therapy. Microbubbles (MB) are effective reflectors of ultrasound and cavitation enhancers, hence their roles in diagnostic and therapeutic ultrasound. MB must be of controlled size, concentration, biocompatible, and stable for biomedical use. Because of low water solubility and high molecular weight, fluorinated gases are generally used to make MB for biomedical applications. Lipids are a viable approach to stabilize MB for use as ultrasound contrast agents. MB of gas can be condensed into nanodroplets or Phase Shift Microbubbles (PSMB). PSMB can remain condensed following vascular administration, but upon application of ultrasound, can reform MB for use as cavitation nuclei. Because of their small size, PSMBs permeate thrombus and tumor microvasculature. Studies have shown effective sonolysis and tumor ablation with PSMB. Lipid-based systems provide robust opportunities for stabilizing MB and PSMB. Improved lipid coating materials are currently in clinical development for novel ultrasound contrast agents. Using the building blocks of lipids and fluorocarbon gases novel platforms are under development for theranostics-a blending of therapy and diagnostics, referring to an integrated medical approach that combines diagnostic imaging and targeted therapy to personalize patient treatment. For example, a theranostic agent might detect a tumor through imaging while simultaneously delivering a therapeutic drug or radiation to the tumor site. This dual functionality enables precise disease characterization, treatment monitoring, and optimized therapeutic outcomes, improving efficacy and reducing side effects. In addition, MB or nanobubbles can be used for oxygen delivery, and these applications will also be reviewed.